There's a big controversy in the dog world today -- at least,
for a vocal minority, it's a big controversy, and it shows some signs of wanting
to spread into the mainstream of show breeders. Everyone concerned with
breeding probably needs to know enough about it to get around in the discussion.
The controversy concerns the systems of inbreeding used to fix and then to
maintain the characteristics of today's purebred dogs. It can be summed up
briefly this way:

Does inbreeding as universally practiced by today's dog fancy
inevitably result in a negative impact on the health of purebred dogs?

I'm assuming that everyone interested in this question already
understands the way the terms "inbreeding", "line breeding", and "outbreeding"
are used by breeders. I won't go into that here in any detail. Just
in case, I shall say briefly: Inbreeding is considered to be the breeding
of close relatives: uncle-niece or closer. Line breeding is
inbreeding, but to a lesser degree: grandfather-granddaughter or further
away, and usually implies that the breeder is trying to maximize the genetic
contribution of one particular ancestor. Precisely where breeders draw the line
between inbreeding and line breeding depends on the breeder and
isn't important for the purposes of this discussion, which assumes that
inbreeding and line breeding are essentially the same.

Outbreeding is frequently taken to mean "no repeated ancestors
within the last five generations." You will find statements all over the
web, and in a lot of books and articles written by and for breeders, that ancestors further back in the pedigree than that have no
important influence and don't count. This is not true, as for example
Jerold Bell shows with his analysis of his Gordan Setter's pedigree.
(The Ins and Outs of Pedigree Analysis; you can find a copy here:
http://www.dogstuff.info/genetic_index.html. ) A standard 5-generation
pedigree can conceal a heck of a lot of "background" inbreeding. Really
the only way to confirm you are outbreeding is to calculate a coefficient of
inbreeding (COI) for your planned breeding, based on at least a
fifteen-generation pedigree (more is better), and you must confirm that this COI
is lower than the average inbreeding coefficient for your breed. The COI
for your "outbred" puppies may still be much, much higher than the average COI
for most natural, non-domestic, populations of animals.

Technically, the only true "outcross" would be to a dog from
another breed. Many purebred dog breeds are descended from a very small
number of ancestors. All were created by closing the gene pool off from
the general run of dogs -- that is why pure breeds have distinct
characteristics. That is why it is accurate to say that all modern
breeds were established and are maintained via inbreeding.

So is inbreeding inherently harmful?

Various advocates of outbreeding will vehemently answer Yes to
this question, and they have a plausible argument to support their position.
The majority, probably, of show breeders who have thought about this issue, will
say No. They, too, have plausible arguments to support this answer.

Actual evidence for either position is in surprisingly short supply.
Assumptions, on the other hand, litter the ground in abundance. The following
is meant to lay out clear hypotheses and to show how data could be collected that
would allow fanciers to evaluate current breeding programs and decide whether
fundamental changes should be made -- for the overall benefit of the breeds they
profess to love.

First, please keep in mind that human beings have a terrible
time assessing objective reality. A teacher will tell you that young Timmy
is ALWAYS out of his chair and ALWAYS disruptive in class -- then, when she
makes actual notes about his behavior, will find that young Timmy was out of his
chair and disruptive only an average of eight times per day, which is about normal
for boys in his class. A gardener will swear that THIS spring is the worst
in memory -- the coldest and rainiest -- but checking actual records shows that
in fact about one spring in three has had comparable weather for the past fifty
years. A neighborhood
will become convinced that the power lines located near their houses are causing their kids to develop leukemia -- when a check of
medical records nationwide reveal that the rates of leukemia for that
neighborhood are precisely normal. This sort of thing happens all the
time. A breeder who asserts that immune disorders have vastly
increased in purebred dog populations in the past few decades is making a
precisely similar assertion.

The ONLY way to know what is happening in populations of
purebred dogs is to keep objective records for decades and then examine them,
keeping in mind that changes in vaccination protocols, incidence of infectious
disease, changes in diet, changes in diagnostic tools, etc, over the same time period, can seriously impact
the data. An emotional
conviction that rates of hip dysplasia, or anything else, have increased in purebred dogs cannot be
taken as proof that this has occurred if no actual data are available for
earlier populations. This is true for all health concerns.
Conviction is not an adequate substitute for facts.

It's quite true that purebreds as they exist today are
historically an anomaly. The closed studbooks that limit the gene pools of
today's pure breeds represent a new kind of breeding attitude. Earlier
than about a hundred years ago, dogs were bred to what might be called "working
standards" and it was perfectly ordinary for a breeder to add a bit of this and
a dab of that during the process of creating his idea of the perfect dog.
This is still how Alaskan huskies are bred -- the sled dogs used for the major
endurance races are not "pure" husky. Breeders of working Alaskan huskies add
pointer and retriever, setter and greyhound, to their working huskies --
whatever their experience leads them to expect should add speed and endurance to
their dogs. And it works. Their dogs do not greatly resemble the
spectacularly beautiful Siberian huskies you will see in the conformation ring.
They are racy, long-legged, lean animals that have no peers for racing -- they beat
Siberian huskies hands down. There is no mammal on Earth that rivals
Alaskan huskies for endurance racing (Coppinger 2001, Dogs).

Alaskan huskies are the sorts of animals that result from
breeding for performance without closing stud books -- and this is the sort of
breeding that historically was common. Livestock guarding dogs, herding
dogs, war dogs, hunting and vermin dogs, lurchers and curs (in the technical
sense of the word) -- these are the original performance breeds. The idea
of closing off a breeding population and breeding an isolated population to a physical standard of
perfection is the new idea in breeding. You will not get that kind of
conception of purebreds as isolated populations in horse breeding, where
crossbreds are purposely produced in great numbers to perform specific functions
(Morabs, Aztecas, lots of "warmbloods", etc.). Nor will you see closed
studbooks in cattle breeding, where large operations deliberately produce
crossbred heifers which they then cross to a bull of still a third breed in order to maximize
fertility and growth rates.

Does it harm dogs to breed them as we do today? The gene
pools are tiny, relatively speaking. All purebred dogs today are inbred.
A mating that looks "outbred" on paper -- to five generations -- will
probably look
inbred if taken back eight or more generations. Jerold Bell (www.compuped.com/bell.htm)
did a pedigree analysis of one of his Gordan setters. This animal was the
product of a first-cousin mating, giving her an inbreeding coefficient of 6.25%.
This is a low level of inbreeding for purebred dogs. However, when her
inbreeding coefficient was recalculated over twelve generations, it was 30.81%,
which is higher than it would have been for a parent-offspring mating (that
would be 25%, of course). Most of this animal's inbreeding was invisible
in a normal pedigree. The dog who provided the single greatest genetic
contribution to this setter (other than her parents) was an ancestor who
appeared first in her pedigree six generations back, and then appeared in the
pedigree 33 times. Bell refers to inbreeding that has been hidden back in
the pedigree as "background" inbreeding. It's clear from his analysis that
background inbreeding can be very high, even for animals that appear outbred to
four or five generations.

What does this do to purebred dogs?

The traditional answer (which may be correct) is: Not
Much. Inbreeding increases homozygosity of alleles at all genetic loci --
everyone agrees on this (the math is simple). Close inbreeding increases
homozygosity fast, whereas looser inbreeding (linebreeding) increases
homozygosity more slowly. Homozygosity per se may not be a huge
concern, however. Deleterious alleles are not created by inbreeding, but
are revealed in the phenotype of the dog when they are present homozygously.
This allows deleterious alleles (the "genetic load" of a breed) to be removed
from the population as they show up, resulting, eventually, in a healthier population -- at
least with respect to those alleles.

The newer answer (which may be correct) is: It Destroys
Disease Resistance. The major histocompatibility complex is a part of the
immune system that is concerned with recognizing foreign antigens. One
reasonable hypothesis is that heterozygosity at MHC loci is essential to allow
an organism to defend itself against the huge diversity of foreign antigens it
will contact throughout its life. Inbreeding, which inevitably decreases
heterozygosity at all loci, is then expected to inevitably reduce disease
resistance. As a secondary effect, or set of effects, inbreeding depression is also
expected to invariably, or almost invariably, reduce fertility, litter size,
growth rates, longevity, and general vigor. These effects, arising from an increase
in homozygosity in more subtle deleterious alleles that do not cause actual
overt disease, are what lead cattle people to crossbreed their livestock.
It seems to work for them, and they're not likely to be wrong -- market forces
have a lot of oomph when it comes to forcing cattle breeders to make
economically sound decisions.

Note that this second idea produces one very clear hypothesis:
the reduction of overall disease resistance should be inevitable and should
always correlate with the degree of homozygosity within a population.
This is a very rigid hypothesis. Note that one counter-example is
sufficient to disprove this hypothesis. The mechanism proposed does not
readily allow for counter-examples to exist, so this hypothesis cannot easily be
re-conceptualized in a less rigid form, such as usuallycorrelates
with or
tendstocorrelate with.

In
addition, the "inbreeding-always-bad" idea produces a second hypothesis:
that the degree of inbreeding should correlate significantly with
reduced fertility, litter sizes, growth rates, longevity, and vigor. This
second hypothesis does not mandate the strength of the expected correlation;
however, it does anticipate always or almost always getting negative correlations of COI with
some or all of these characteristics.

These hypotheses are distinct. One could be true while the
other is false. Data that support one hypothesis should not be taken as
also supporting the other.

You can calculate the degree of inbreeding as the COI -- the
coefficient of inbreeding. Theoretically, it should be possible to get
records from scrupulously-honest long-time breeders who have produced lots of
puppies and tracked their health carefully in objective ways, calculate the COI for each of the
animals they have produced, and check for correlations.

Lacking such data sets, is it possible to evaluate these
hypotheses?

Well, it is, sort of. For the first hypothesis, what we need to look for
particularly is evidence that tight inbreeding does not inevitably lead to the
failure of a population, preferably in dog, or at least canid, populations, but
any population will do because the MHC hypothesis is so clear-cut.

What does a literature survey show us? The lack of a large
university library in my neighborhood is a problem, but here's what I've found
so far that seems to address this problem:

1. Population bottlenecks in cheetahs have
resulted in the creation of an extremely inbred species, as is well-known. Effective
population sizes in the wild are even smaller than they would appear from the
number of animals actually in the populations. Although reproductive
success in captive cheetah populations is very poor, and this has been
attributed to the extreme lack of genetic variability in the species (and this
attribution has been made in the popular press, so the idea has gained more
visibility than is, perhaps, ideal), reproductive success in the wild is
actually very
good. Wild cheetahs do not differ significantly from captive animals in
terms of how closely they are inbred, so the inbreeding hypothesis cannot be the
correct explanation for lack of captive-breeding success. A high fraction
of sperm in cheetahs is malformed, and this may be due to inbreeding, but the
good reproductive success in the wild again indicates this is not important.
Wild cheetahs do not show other effects considered typical of inbreeding, such
as reduced litter sizes. MHC loci retain some heterozygosity in cheetahs
and there have not been any major disease epidemics in wild populations in
recent history.

2. Ellegren et al. describe a severely
bottlenecked population of beaver, which recovered with no or very little
apparent effect from inbreeding. These beaver are, very interestingly, monomorphic (homozygous) for MHC loci. Even a comparison population with
lots of genetic variability in general was still homozygous for MHC loci.
Ellegren et al. suggest that beaver may be tolerant of inbreeding because of
their population dynamics, which require dispersal along waterways and thus
restrict chances for outbreeding. The authors also note that beaver appear
to lack behavioral mechanisms that would serve to reduce inbreeding -- that is,
they do not hesitate to mate with close relatives.

3. Mates in a wild population of shrews were
more related than chance would have dictated for the population, implying that
these animals prefer or were compelled by ecological factors to choose mates that
were related to themselves.
Relatedness had no effect on fecundity and offspring homozygosity had no effect
on their ensuing reproductive success. This one is from an Orals Poster I
got off the internet, so it's not based on a massive, detailed collection of
data; however, the result reported is definitely suggestive.

4. In captive Indian rhinos, inbreeding vs. outbreeding
effects were examined for correlation with gestation period, birth mass, infant
mortality, and growth of the offspring. Inbred calves produced by matings
between rhinos from a strongly inbred and highly homozygous population grew more
slowly but suffered less mortality than non-inbred or outbred (mates, in this
case, from very
distinct populations) calves. Inbreeding did not effect gestation period
or birth mass.

6. There is (surprise!) a vertebrate species which
self-fertilizes, normally the province of plants! Who knew? This
animal, a killifish (Rivulus marmoratus), is a very plentiful and widely
dispersed species which is found in coastal mangrove swamps, in marine or
brackish environments. It's an interesting little critter ecologically,
but most interesting is its reproductive biology. Most individuals of
R. marmoratus are hermaphrodites (a few are male in some populations) and
obligately self-fertilizing. Three histocompatibility clones appear to
exist. Individuals are highly homozygous, of course. Fitness traits
of lab-produced heterozygotes have not been compared to natural homozygotes
because of the considerable difficulty in getting clonal individuals to
outcross. There is no evidence for inbreeding depression in this species,
which is by all accounts very successful.
It seems clear, also, that MHC monomorphism cannot be a problem in this species.

How relevant is all this to dogs? Good question. It
seems very likely that at least some species do okay even under very strong
inbreeding regimes. Other areas to look for data would be in studies of
pond fishes, plateau animals, island populations, and other natural populations
that must be subject to fairly strong inbreeding. Meanwhile:

7. The very strongly inbred population of
Isle Royale wolves was thought, up until 1993, to be succumbing to inbreeding
depression and bad luck. However, they have bounced back dramatically
since then, assisted by a bad year for moose that allowed them to kill prey
animals more easily. There are no signs of disease or genetic problems in
the Isle Royale wolves, although there is some evidence of skeletal asymmetry,
which is thought to be an effect of inbreeding. Nor have signs of
inbreeding depression been found in a captive population of Mexican grey wolves
arising from seven founders. Moreover, wolves have been observed
to naturally inbreed (prefer closely related mates) in at least some natural populations.
Further,
severely inbred populations that may have been suffering from reduced
reproductive success appear to need very little immigration to rebound strongly.

Mech, L.D. 1970.
The Wolf: The Ecology and Behavior of an Endangered Species. The
Natural History Press, Garden City, NY. 384 p.

Shields, W.M. 1983.
Genetic considerations in the management of the wolf and other large
vertebrates: an alternative view. Pp. 90-92. In: Carbyn, L.N. (ed.). Wolves in
Canada and Alaska. Canadian Wildlife Service Report Series No 45.

Vila et al.
2002. Rescue of a severely bottlenecked wolf population by a single
immigrant. Proc R Soc Lond.

8. Willis, in his book Genetics of the
Dog, has a chapter about inbreeding. In this chapter, he mentions
(with citations, of course) several populations of rats and cattle that did fine
with very intense inbreeding. One population of rats was taken through 25
generations of brother-sister matings without ever compromising its vigor or
fertility -- or clearly, its disease resistance. Somebody would probably have
noticed if all the rats had died of infectious diseases halfway through the
experiment. Following is a citation for the rat study, which I haven't seen
personally, plus a more extensive description:

9. King, H. D. 1919. Studies on
inbreeding. 175 pp. Reprinted from the May, July, and October (1918)
and August (1919) issues of the J. of Experimental Zoeology. [That's not
my typo -- it's really spelled that way in the reference I found] King examined the effects of inbreeding on growth, body
weight, fertility, "constitutional vigor," and sex ratio of the standard albino
lab rat. The intensely inbred line (and it was intensely inbred)
prospered in every way -- King evidently practiced strong selection for
desirable traits (large size, large litter size, health). Note that it
doesn't matter how much culling King had to do to achieve her results --
homozygosity was the inevitable result of the very intense inbreeding practiced
and homozygosity alone did not destroy the line. Despite the date on her
work, it deserves respect, as King evidently received very high honors indeed
for a female scientist of that era (
http://www.amphilsoc.org/library/mendel/1998.htm ).

So, what's the answer to the questions about inbreeding in
purebred dogs?

Good question.

Inbreeding cannotpossiblyleadinvariably to disease susceptibility,
via an increase in homozygosity of the MHC. If
this chain of causal events was correct, then the results we observe in some of
the reports cited above (especially the beaver and killifish studies) could not
occur. The
beaver populations, monomorphic (homozygous) for MHC loci, specifically drive a
stake through the heart of the idea that MHC diversity is always crucial
to maintaining a healthy population. This hypothesis must be oversimplified at
best and wrong at worst. We do not know what effect MHC homozygosity will
have or is having on purebred dogs. We will not and cannot answer this more
specific question until actual data on dog populations are collected in a
sufficiently rigorous manner to allow such an answer.

Inbreeding cannotpossiblyleadinvariably to a
decrease in litter size, fertility, longevity, birth weight, and general vigor.
If it did, we could not see a failure of these expectations for cheetahs,
beaver, rhinos, shrews, captive wolves, etc. On the other hand, frequently
inbreeding depression does correlate with at least one of these
expectations, as we see in cattle and in innumerable studies of natural and
managed populations.

There are many observations dog breeders have made that may
support the idea that inbreeding depression may sometimes negatively influence
various reproductive and other characteristics of dogs.

Mary Roslin Williams, in
her book Reaching for the Stars, commented that litter sizes in labs had
declined dramatically during the years she had been breeding (she did not
suggest, and would almost certainly disagree with, the idea that inbreeding is fundamentally a flawed breeding system).

Grossman &
Grossman, in their book Winning with Purebred Dogs, noted that they never
had problems with puppy mortality (fading puppy syndrome) during their early
years of breeding. They hypothesized that inbreeding had led to their
eventual problems with mortality and reported an outcross which yielded a litter
that did not experience mortality. Their sample size is far too small to
allow reliable conclusions. Their comments that other breeders had
reported the same pattern certainly suffers from the unreliablity of human beings
in perceiving what is actually going on, whether the observation is in fact
accurate or not. That is, once a breeder personally experiences a
particular problem, than he is certainly more likely to note other instances of
that problem in the future, regardless of how frequently the problem actually
occurs. This is precisely similar, for example, to Oliver Sacks becoming interested in Tourette's syndrome after finding one patient with the syndrome and then
immediately spotting numerous cases of Tourette's "on the street". This
sort of problem is why somebody's impression of a phenomenon is no
substitute for rigorously-collected data.

Longevity was negatively correlated with increasing COI in one
analysis done on Rhodesian ridgebacks (www.andycheah.com/files/RRLongevity.pdf
), but I don't know about the sample size or methodology for that analysis.
A similar correlation was found by Armstrong for standard poodles (
http://www.canine-genetics.com/lifespan.html ), Armstrong being
one of the more high-profile proponents for outbreeding, and even out-crossing,
purebred dogs. Comparisons between standard poodles and Clumber spaniels
found that the (more inbred) Clumbers live on average shorter lives than the
(less inbred) Standards. Of course, Clumber spaniels are physically very,
very different from standard poodles! If the physical characteristics of
Clumber spaniels turn out to generally decrease lifespan, which is very
plausible, then where does this leave that result? It would be
interesting, and far more realistic, to see a comparison between more physically
similar breeds, or between inbred and outbred animals within one breed.

Many breeders, not to mention random people you meet around and
about, will tell you that health problems are on the rise
and will go on to blame these problems on inbreeding. Data
supporting the link between inbreeding and disease susceptibility are lacking in
purebred dogs, however common opinions may be. Data from
natural populations of vertebrate species indicate that the inevitableness of
this link is, at best, highly questionable. My best guess is that we will
find, during the next decade or so, that the connection between MHC
heterozygosity and disease resistance is more
complex than is currently assumed.

On the other hand, links between inbreeding, high COI, and
problems with fertility, litter size, longevity, birth weight, and / or general
vigor may be more strongly supported (although not universally so; see the rats,
above). Conviction alone does not equal
support. When breeders (
http://www.everythinggolden.com/ conformation.htm ) offer examples of animals with low COI that are nevertheless outstanding in the
show ring and as producers, that is nice, but it does not provide evidence
to support any position whatsoever. You need to know what proportion
of top winners and producers have low vs. high COIs, not whether it's possible
to get a top winner / producer who has a low COI.

An interested breeder might be able to generate such evidence (or
counter-evidence -- you don't know till you look what you're going to get) by
taking a random list of 100 top winners vs. 100 mediocre animals and seeing how
many of each group had low vs. high COI -- keeping in mind that COI for a
five-generation pedigree will be less than for a ten-generation pedigree.
This data set could be confounded by breeding systems if most breeders who
produce top winners also inbreed heavily and most who don't, don't. Winners may not be good
producers, so that's a separate analysis. Or, you could get a list from
several top breeders of animals with high COI vs. animals with low COI and see
what proportion of each group went on to be top winners and producers.
This data set could be confounded if breeder expectations for and investment in
high-COI animals tended to be greater than for low-COI animals. There are
ways to work around problems with data sets, but thinking through possible
problems with your data is crucial, preferably before you draw
conclusions.

Easier to generate are data relevant to whether low COI
correlates with longevity, litter size, fertility, and health. It would perhaps
be wise to separate health out into separate categories once you get your data
set in hand: autoimmune problems. Polygenic problems. Simple
genetic problems. Structural defects. Susceptibility to infectious
disease. Etc. You get this kind of data with comprehensive breed
surveys, valuable for many reasons. Looking at longevity via surveys is
somewhat difficult because people who have owned dogs for a long time may forget
about dogs that died young when generating lists of dogs and their ages at
death. Also, a data set which excludes still-living dogs while including
their dead age-mates will underestimate longevity, perhaps seriously. Even
harder to examine is a possible link between high COI and reduced vigor.
(Define "vigor".)

Notice, by the way, that if you look at twenty different
possible correlations between COI and canine characteristics, that you are
likely to get one result that is significant at the p = .05 level by
accident (that is, it is not really significant). That is what
"significant at the p = .05 level" means -- that there is a five percent (1 in
20) probability that the "significance" you think you see occurred by chance
alone.

If all this seems complicated, I can't help that. The
subject is rife with complicating factors. The take-home message, I
suppose, ought to include the understanding that MHC homozygosity definitely
cannot inextricably be linked to immune dysfunction. And that you need to
be careful to look at the methodology underlying assertions before accepting
them. And that subjective impressions about canine health and genetics, no
matter how strongly believed, are sometimes a desperately poor guide to what
really is going on. That one is always a problem, in all aspects of life.
And -- most important -- that a careful breeder who keeps meticulous records may
be able to add a heck of a lot to this discussion.